Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000229382 | SCV000290769 | uncertain significance | Parathyroid carcinoma | 2024-07-30 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 263 of the CDC73 protein (p.Arg263Cys). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with primary hyperparathyroidism (PMID: 28870973). ClinVar contains an entry for this variant (Variation ID: 241497). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CDC73 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002411061 | SCV002675568 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-02 | criteria provided, single submitter | clinical testing | The p.R263C variant (also known as c.787C>T), located in coding exon 8 of the CDC73 gene, results from a C to T substitution at nucleotide position 787. The arginine at codon 263 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration was detected in an individual with primary hyperparathyroidism (Mamedova E et al. Endocr Connect, 2017 Nov;6:557-565). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003463681 | SCV004215591 | uncertain significance | Hyperparathyroidism 1 | 2023-05-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004816446 | SCV005439299 | uncertain significance | not provided | 2024-06-18 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 15923622, 15632063, 38396977, 28870973) |